HUMORAL IMMUNE-RESPONSES IN VOLUNTEERS IMMUNIZED WITH IRRADIATED PLASMODIUM-FALCIPARUM SPOROZOITES
HUMORAL IMMUNE-RESPONSES IN VOLUNTEERS IMMUNIZED WITH IRRADIATED PLASMODIUM-FALCIPARUM SPOROZOITES
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DOI：
10.4269/ajtmh.1993.49.166
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发表时间：
1993-08-01
影响因子：
3.3
通讯作者：
GORDON, DM
中科院分区：
文献类型：
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作者：
EGAN, JE;HOFFMAN, SL;GORDON, DM
接受伽玛辐照恶性疟原虫孢子体免疫的志愿者可作为抗蚊媒疟疾传播保护性免疫的金标准，为研究保护性免疫效应机制提供了相关模型。在7-12个月的时间里，我们通过辐射感染蚊子的叮咬给四名志愿者接种了疫苗。在暴露于减毒孢子虫之后，所有四名志愿者都产生了针对孢子虫的抗体，通过免疫荧光测定和酶联免疫吸附测定，使用环孢子虫（CS）蛋白重复分子R32LR作为捕获抗原。三名志愿者还开发了针对CS蛋白非重复（侧翼）区域的抗体；在体外实验中，这些抗体水平与血清活性平行，抑制肝癌细胞孢子子的侵袭。这三名志愿者受到保护，不受5只受感染蚊子叮咬传播的疟疾的侵害。其中两名受保护的志愿者接受了额外免疫剂量的辐照孢子子，随后受到了异源恶性疟原虫克隆的保护。在本研究过程中，未观察到循环中肿瘤坏死因子、干扰素- γ或白细胞介素-6水平的可检测波动。对这些受保护志愿者的体液和细胞免疫反应的分析有望为针对疟疾寄生虫红细胞前阶段的其他免疫靶点提供重要线索。
Volunteers immunized with gamma-irradiated Plasmodium falciparum sporozoites serve as the gold standard for protective immunity against mosquito-borne malaria transmission and provide a relevant model for studying protective immune effector mechanisms. During a 7-12-month period, we immunized four volunteers via the bites of irradiated, infected mosquitoes. Following these exposures to attentuated sporozoites, all four volunteers developed antibodies to sporozoites as measured by an immunofluorescence assay and by an enzyme-linked immunosorbent assay using the circumsporozoite (CS) protein repeat-based molecule R32LR as capture antigen. Three volunteers also developed antibodies against the nonrepeating (flanking) regions of the CS protein; the level of these antibodies paralleled the serum activity to inhibit sporozoite invasion of hepatoma cells in vitro. These three volunteers were protected against malaria transmitted by the bites of five infected mosquitoes. Two of these protected volunteers received additional immunizing doses of irradiated sporozoites and were subsequently protected against challenge with a heterologous P. falciparum clone. No detectable fluctuations were observed in circulating levels of tumor necrosis factor, interferon-gamma, or interleukin-6 during the course of this study. Analysis of the humoral and cellular immune responses of these protected volunteers is expected to yield important clues to additional targets of immunity against the pre-erythrocytic stages of malaria parasites.